((3As,5r,6s,6as)-6-hydroxy-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)(morpholino)methanone → (3-(4-(benzyloxy)benzyl)-4-methylphenyl)((3aS,5R,6S,6aS)-6-hydroxy-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)methanone

HRID 1499303Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1499303
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]([C:17]2[CH:22]=[C:21](Br)[CH:20]=[CH:19][C:18]=2[CH3:24])O)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.[OH:30][C@H:31]1[C@H:38]2[C@H:34]([O:35][C:36]([CH3:40])([CH3:39])[O:37]2)[O:33][C@H:32]1[C:41](N1CCOCC1)=[O:42].C([Mg]Cl)(C)(C)C>C1COCC1>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:17]2[CH:22]=[C:21]([C:41]([C@@H:32]3[O:33][C@H:34]4[O:35][C:36]([CH3:40])([CH3:39])[O:37][C@H:38]4[C@@H:31]3[OH:30])=[O:42])[CH:20]=[CH:19][C:18]=2[CH3:24])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Komponenten

6

Edukt 4

HCID 25207258((3As,5r,6s,6as)-6-hydroxy-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)(morpholino)methanoneHCID 90177007(4-(Benzyloxy)phenyl)(5-bromo-2-methylphenyl)methanolHCID 178418310HCID 178418310, VerbindungHCID 178418339Butyllithium

Produkt 1

HCID 90177932(3-(4-(benzyloxy)benzyl)-4-methylphenyl)((3aS,5R,6S,6aS)-6-hydroxy-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)methanoneAusbeute 70 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

To a solution of 2-(4-(benzyloxy)benzyl)-4-bromo-1-methylbenzene (34, 2.71 g, 7.4 mmol) in THF (37 mL) under nitrogen at −78° C. was slowly added n-butyllithium (3.3 mL of 2.5 M solution in hexanes, 8.1 mmol), and the reaction was stirred for 30 min. Meanwhile, to a solution of ((3aS,5R,6S,6aS)-6-hydroxy-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)(morpholino)methanone (2.02 g, 7.4 mmol) in THF (37 mL) under nitrogen at 0° C. was added tert-butylmagnesium chloride (8.1 mL of 1 M solution in THF, 8.1 mmol). The reaction was stirred for 20 min, then added slowly by cannula to the aryl lithium solution at −78° C. The reaction was allowed to gradually warm to room temperature over 3 hours, then quenched with saturated aqueous NH4Cl, diluted with EtOAc, washed with H2O and brine (with back extraction), dried over MgSO4, filtered, and concentrated under vacuum. The residue was purified by silica gel flash chromatography (gradient 0-50% EtOAc/hexanes) to give 2.44 g (70% yield) of the product 35 as a white foam. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.86 (dd, J=7.8, 1.8 Hz, 1 H), 7.75-7.80 (m, 1 H), 7.27-7.49 (m, 6 H), 7.04 (d, J=8.6 Hz, 2 H), 6.86-6.96 (m, 2 H), 6.09 (d, J=3.5 Hz, 1 H), 5.32 (d, J=2.8 Hz, 1 H), 5.04 (s, 2 H), 4.60 (d, J=3.5 Hz, 1H), 4.53-4.58 (m, 1 H), 3.98 (s, 2 H), 3.03 (d, J=4.3 Hz, 1 H), 2.31 (s, 3 H), 1.56 (s, 3 H), 1.36 (s, 3 H); MS (ES+) [M+H]+=475.

Aufarbeitung

  1. customat −78° C.
  2. stirringThe reaction was stirred for 20 min
  3. customquenched with saturated aqueous NH4Cl
  4. additiondiluted with EtOAc
  5. washwashed with H2O and brine (with back extraction)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. customThe residue was purified by silica gel flash chromatography (gradient 0-50% EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-347b864c7bba4e43b96c1fead0274daf
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09200025B2

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